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Biomedical subjects

A Hoffman

Publications and source records attributed to A Hoffman.

At least 181 records · Page 10Linked to original sources
PubMed1991

Use of a monoclonal antibody enzyme-linked immunosorbent assay to measure human respiratory glycoprotein production in vitro.

High-molecular-weight glycoprotein from human airway cultures was used to generate murine monoclonal antibodies, one of which recognizes a high-molecular-weight, hyaluronidase-resistant glycoprotein localized by immunofluorescent microscopy and immunogold electron microscopy to the secretory granules of human airway submucosal gland mucous cells and goblet cells. This monoclonal antibody was used to develop an enzyme-linked immunosorbent assay (ELISA) that was adapted to the study of respiratory glycoprotein secretion from human airways in vitro. Using the assay, the effect of a known mucus secretagogue, the cholinergic agonist methacholine, was studied on explant cultures of tissue from human bronchus or from human nasal mucosa. In studies of human bronchus explants, methacholine, 100 and 10 microM, stimulated increased secretion of respiratory glycoprotein (RGP) by 109 +/- 8% (n = 14; P less than 0.001) and 96 +/- 14% (n = 9; P less than 0.001), respectively, above control values. In studies of human nasal turbinate mucosal explants, methacholine, 100 and 10 microM, stimulated increased secretion of RGP by 75 +/- 28% (n = 7; P less than 0.01) and 70 +/- 21% (n = 4; P less than 0.01) above control values. An ELISA for the measurement of RGP secretion may provide a sensitive and more specific method for the performance of in vitro studies of RGP secretion from human tissues.

Animals↗
PubMed1991

Six years of occult blood screening in an urban public hospital: concepts, methods, and reflections on approaches to reducing avoidable mortality among black Americans.

While early cancer detection is frequently overused in high socioeconomic status communities, opportunities for early detection often are overlooked by practitioners serving lower income and minority populations. Review of our patient records in 1980 revealed that only 13% of patients had a record of a rectal examination, and less than 1% had either proctoscopy or fecal occult blood testing. Our program has made a dramatic impact on colorectal cancer detection, performing 8192 fecal occult blood tests in the first 5 1/2 years of our program. As with other programs, stage of cancer is greatly influenced by fecal occult blood testing, with 0 modified Dukes' stage D compared to 33% for the hospital registry, and 35% stage A compared to 0 for the registry. Compliance with diagnostic evaluation has been excellent (89.6%). The program has allowed for increased communication between patients and staff. Education about diet and other prevention has been institutionalized. Patients see our nurses as their advocates and openly express their fears and concerns about their health and health care. We began our fecal occult blood testing program at a time when it was considered the "standard of care" although randomized clinical trial proof was, and is, incomplete. This program provides evidence that "standard of care" is feasible in the public sector.

Black or African American↗
PubMed1991

Enhanced interstitial fluid adenosine attenuates myocardial stunning.

Reversible myocardial dysfunction associated with transient ischemia has been termed the stunned myocardium. Because exogenous adenosine has been shown to protect the ischemic myocardium, we hypothesized that augmentation of endogenous adenosine levels would attenuate myocardial stunning. To induce stunning, anesthetized dogs were subjected to 15 minutes of ischemia (left anterior descending artery occlusion) followed by 60 minutes of reperfusion. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 5 mg/kg/hr), an adenosine deaminase inhibitor, was used to augment adenosine levels. The effect of EHNA on interstitial fluid (ISF) adenosine levels, coronary blood flow, and regional systolic wall thickening was compared with that of an untreated group (n = 8). EHNA increased preischemia ISF adenosine levels threefold and was associated with a corresponding increase in coronary blood flow. EHNA administration did not alter preischemia systolic wall thickening. Although ISF adenosine increased fourfold during ischemia in the untreated group, ISF adenosine increased nearly sixtyfold above preischemia values in the EHNA-treated group and remained elevated throughout reperfusion. Postischemic regional function was enhanced significantly in the group treated with EHNA. These data show that adenosine deaminase inhibition increased ISF adenosine levels and attenuated myocardial stunning. Metabolic manipulation of myocardial ISF nucleoside levels may be beneficial in limiting postischemic myocardial dysfunction.

Adenine↗
PubMed1991

Presence of immunoreactive endothelin in synovial fluid: analysis of 22 cases.

The endothelins are a family of recently defined active peptides with a wide range of activities, including the activation of the synthesis of prostaglandins. The concentration of endothelin in inflammatory and noninflammatory synovial fluids (SF) was measured by a sensitive radioimmunoassay. Endothelin-like immunoreactivity was detectable in all SF samples and the mean concentration of endothelin was 2.6 +/- 0.3 pg/ml, more than twice that in normal human plasma. The mean level of endothelin in SF in rheumatoid arthritis was 2.5 +/- 0.4 pg/ml (n = 11), and was not statistically different from either osteoarthritis, 3.0 +/- 0.5 pg/ml (n = 7), or acute inflammatory arthritis, 2.0 +/- 0.4 pg/ml (n = 4). Our data do not support the hypothesis that endothelin plays an important role in the pathogenesis of inflammatory arthritis.

Aged↗
PubMed1990

Highly conserved core domain and unique N terminus with presumptive regulatory motifs in a human TATA factor (TFIID).

The factor TFIID is one of several general factors that are necessary and sufficient for transcription initiation by mammalian RNA polymerase II. Stable interactions with the common TATA element lead both to template commitment and to the assembly of the other general factors into a functional preinitiation complex. Consistent with its key role in the promoter activation pathway, human TFIID also seems to be a target for some regulatory factors, as evidenced both by physical and functional studies of interactions between these components. The evolutionary conservation of functional properties led to the purification and cloning of yeast TFIID, the identification of presumptive structural motifs, and direct structure-function studies. Here we report the cloning of a complementary DNA encoding a functional human TFIID. This reveals an evolutionarily conserved core which corresponds precisely to the 180-residue DNA binding/activation domain determined for yeast TFIID, a near absolute conservation of component structural motifs (direct repeats, central basic core/lysine repeat, and sigma homology), providing further support for their functional importance, and a unique N-terminal structure that suggests involvement in species-specific regulatory factor interactions.

Amino Acid Sequence↗
PubMed1990

Opposite effects of endothelin-1 and Big-endothelin-(1-39) on renal function in rats.

Bolus injections of Big-endothelin-(1-39) (Big-ET; 0.1-3.0 nmol/kg) induced a dose-dependent diuretic and natriuretic response in conscious Sprague-Dawley rats. Endothelin-1-(1-21) (ET-1; 1 nmol/kg) induced an opposite effect with almost complete renal shut down. Renal blood flow did not change with Big-ET but was reduced by half with ET-1. Although the maximal pressor responses of the two peptides were comparable the renal resistance did not change with Big-ET but increased 4-fold with ET-1. These data suggest that Big-ET may have a different mechanism of action than ET-1.

Anesthesia↗
PubMed1990

Liquid chromatography/time-of-flight mass spectrometry with high-speed integrated transient recording.

High-performance liquid chromatography (HPLC) has been interfaced to a time-of-flight mass spectrometer. The interface is a continuous flow probe and ions are desorbed from the liquid matrix by energetic ion bombardment. Pulsed and delayed ion extraction from the source permits the use of broad ionization times, results in the production of analog signals in each time-of-flight cycle, and provides both energy and spatial focusing. A high-speed integrated transient recording system has been developed and is also reported. This instrument is the prototype for development of a high-speed, high-mass range LC detector with high duty cycle. Its performance is demonstrated for the separation of several mixtures of small peptides.

Amino Acid Sequence↗
PubMed1990

Kinetics of drug action in disease states. XXXVI: Effect of cyclosporine on the pharmacodynamics and pharmacokinetics of a barbiturate (heptabarbital) in rats.

Pretreatment with cyclosporine reportedly prolongs the effect of certain general anesthetics in humans and the sleeping time of mice after pentobarbital administration. This investigation was designed to determine the mechanism(s) of the cyclosporine-barbiturate interaction. Adult female Wistar rats received cyclosporine (50 mg/kg im) or saline solution daily for 3 days. On the third day, they were injected with heptabarbital (45 mg/kg iv). Other cyclosporine-treated and control groups were infused with heptabarbital until they lost their righting reflex. Treatment for 3 d with cyclosporine was associated with decreased rectal temperature, decreased magnesium concentrations in serum and CSF, increased serum creatinine and urea nitrogen concentrations, elevated serum aspartate aminotransferase activity and total bilirubin concentration, decreased serum total protein concentration, and increased hematocrit. These physiologic changes are consistent with the clinically observed hypomagnesemia, nephrotoxicity, and hepatotoxicity in patients treated with cyclosporine. Control rats slept for 90 +/- 14 min (mean +/- SD, n = 9) after heptabarbital injection, whereas cyclosporine-pretreated rats slept for 154 +/- 22 min. Compared with controls, cyclosporine-pretreated rats awoke (after heptabarbital injection) and went to sleep (after heptabarbital infusion) with significantly lower barbiturate concentrations in serum and CSF. Pretreatment with a single 60-mg/kg im dose of cyclosporine 2 h before heptabarbital infusion caused no significant biochemical changes approximately 160 min later, except for elevated serum aspartate aminotransferase (which occurred also after injection of the surfactant-containing vehicle) and serum bilirubin. Again, heptabarbital concentrations at onset of sleep (loss of righting reflex) in serum, brain, and CSF of cyclosporine-treated rats were significantly lower than in saline-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Kinetics of drug action in disease states. XXXIX. Effect of orally administered activated charcoal on the hypnotic activity of phenobarbital and the neurotoxicity of theophylline administered intravenously to rats with renal failure.

The central nervous system (CNS) sensitivity to the hypnotic (general anesthetic) action of phenobarbital and to the neurotoxic (convulsive) action of theophylline is greater in rats with acute renal failure than in normal animals, consistent with clinical observations. In the case of phenobarbital, this increased sensitivity can be produced in normal rats by infusion of a solution of the lyophilized dialysate of serum from rats with renal failure. It was hypothesized that the relevant constituent(s) of this dialysate may circulate between the blood and the intestinal lumen and that it (they) can be adsorbed by orally administered activated charcoal and thereby removed from the body. If so, treatment of renal failure rats with activated charcoal should partly reverse the increased CNS sensitivity to phenobarbital and to other drugs similarly affected. Accordingly, rats with renal failure produced by bilateral ligation of ureters were given an aqueous suspension of activated charcoal, about 1 g per kg body weight, orally every 8 hr for six doses. Uremic controls received equal volumes of water. About 2 hr after the last dose, the animals were infused i.v. with phenobarbital to onset of loss of righting reflex or with theophylline to onset of maximal seizures. In the phenobarbital study, charcoal treatment partly reversed the hypothermia associated with renal failure and caused a reduction of creatinine and total bilirubin concentrations in serum. The cerebrospinal fluid (CSF) concentration of phenobarbital at onset of loss of the righting reflex was significantly higher in charcoal treated rats than in their controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Increased spillover of dopa into arterial blood during dietary salt loading.

1. We measured urinary excretion rates of dopamine (3,4-dihydroxyphenethylamine) and dopa (3,4-dihydroxyphenylalanine) and the spillover rate of dopa into arterial blood during dietary salt loading in conscious Dahl salt-sensitive and salt-resistant rats with intact or denervated kidneys. 2. Dopa spillover was calculated from the steady-state clearance of intravenously infused L-[3H]dopa and arterial levels of endogenous dopa. 3. Daily excretion rates of dopa and dopamine increased by about sixfold during salt loading in both rat strains. Bilateral renal denervation delayed these increases and the natriuretic responses. 4. During dietary salt loading, dopa spillover increased to approximately the same extent as simultaneously measured dopamine excretion. 5. The results suggest that increases in urinary excretion of dopamine during dietary salt loading can be accounted for by increases in the release of dopa into the bloodstream and that the renal nerves contribute to the dopa and dopamine excretory responses.

Animals↗
PubMed1990

Conscious atrial appendectomized rats have a blunted atrial natriuretic factor release to volume expansion but normal responses to other acute stimuli.

The release of atrial natriuretic factor (ANF) after various acute stimuli was studied in conscious chronic bilaterally atrial appendectomized (APP) rats. The response to acute volume expansion was markedly blunted (+67% v +357% in controls, P less than .01). However, the response to norepinephrine infusion was only moderately reduced (+107% v +212%, P less than .05) and the response to acute salt load was identical to that in normal controls (+148% v +180%, P = NS). These results demonstrate that APP rats can increase the secretion of ANF, at least to some acute stimuli. This indicates that the stores of ANF available for release are not significantly depleted after atrial appendectomy.

Animals↗
PubMed1990

The initial vasodilation and the later vasoconstriction of endothelin-1 are selective to specific vascular beds.

The regional hemodynamic effects of endothelin-1 (ET-1) were studied in Wistar-Kyoto rats. Endothelin-1 caused a transient increase in blood flow in the carotid and femoral arteries but a decrease in flow in the renal and mesenteric arteries. The resistance in the carotid and femoral beds decreased while it increased in the renal and mesenteric beds. Subsequently there was a variable increase in resistance in all vascular beds with a maximal increase in the renal bed. Thus, ET-1 initially causes a selective vasorelaxation in musculocutaneous beds but not in visceral beds; the cause of this selectivity is unknown.

Animals↗
PubMed1990

Persistent arteriolar constriction in microcirculation of the terminal ileum following moderate hemorrhagic hypovolemia and volume restoration.

A stable in vivo preparation of moderate hypovolemia with prompt volume restoration was produced in anesthetized rats. The microcirculation of the terminal ileum was observed in vivo videomicroscopy, and changes in mean arterial pressure (MAP) as well as arteriolar diameters were recorded after a 30-min period in which the MAP was reduced by 50% by bleeding. Volume was restored with shed blood alone (control); dextran 70 alone (dextran); or dextran + hypertonic (7.5%) saline (dextran + HS). A final group of rats was pretreated with allopurinol 5 mg/kg and then treated identically to the control group to assess the role of the xanthine oxidase system in microcirculation changes following hemorrhage. MAP was restored to normal by return of shed blood in control animals, but inflow arterioles (A1) remained significantly constricted. MAP was significantly higher and A1 arteriolar dilation was observed in the dextran + HS group. Responses in allopurinol-pretreated animals were not different from the responses seen in control animals. We conclude that persistent arteriolar constriction is produced by moderate hypovolemia and this effect is ameliorated by volume restoration with dextran + HS.

Allopurinol↗
PubMed1990

Sodium intake modulates renal vascular reactivity to endothelin-1 in Dahl rats.

1. The systemic and renal haemodynamic responses to endothelin-1 (ET1) were evaluated and compared to Angiotensin II (AII) in anaesthetized Dahl salt-sensitive (DS) and salt-resistant (DR) rats on either low (0.1% NaCl in diet) or high (8% NaCl in diet) salt intake. 2. Baseline mean arterial pressure on low salt diet was similar in both strains, while on high salt diet it was 73 +/- 4 mmHg in DR rats and 119 +/- 8 mmHg in DS rats (P less than 0.05). Baseline renal blood flow (RBF) and renal vascular resistance (RVR) were similar in all groups. 3. AII in bolus injection induced a short, dose-dependent increase in blood pressure and renal vascular resistance and a fall in renal blood flow. The maximal pressure increase was significantly greater in DS rats on high salt diet than that in each of the other groups (P less than 0.05). The fall in renal blood flow and the increase in renal vascular resistance were attenuated in both strains on low salt diet. 4. ET1 induced an initial decrease followed by a prolonged increase in blood pressure; both phases were similar in all groups. However, renal vascular reactivity to ET1 was markedly modulated by salt intake. On low salt diet, following a bolus injection of ET1 (1 nmol/kg), RBF decreased by 34% in DR and by 20% in DS rats, while on high salt diet RBF decreased by 76% in DR and by 80% in DS rats (P less than 0.05 high vs low salt).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1990

Endothelin-induced vasoconstriction and release of atrial natriuretic peptides in the rat.

Endothelin-1 (ET-1) was given to male Sprague-Dawley rats in i.v. bolus injections to evaluate its effects on blood pressure and the release of atrial natriuretic peptides (ANP). In awake rats ET-1 (0.3, 1 and 3 nmol kg-1 body wt) transiently reduced mean arterial pressure (MAP) and increased heart rate (HR), followed by a prolonged increase in MAP. The magnitude of these changes and the duration of the increase in MAP were dose-related. The increase in MAP was completely blocked by verapamil, reversed by sodium nitroprusside, slightly reduced by rat atrial natriuretic factor (103-126) and unaffected by saralasin. The initial fall in MAP was also unaltered by these agents. In all groups HR changes were mirror-images of MAP. In anaesthetized rats ET-1 (1 nmol kg-1 body wt) induced a sustained release of ANP. Right atrial pressure increased transiently and then fell below baseline. When the increase in MAP was blocked with sodium nitroprusside, ET-1 still produced an increase in ANP. In conclusion we find that repeated i.v. administration of ET-1 induces immediate vasodilatation, without signs of tachyphylaxis, followed by long-lasting severe vasoconstriction. Baroreceptor function seems to be unchanged. ET-1 appears to induce ANP release by a direct action on atrial myocytes, independent of right atrial and systemic arterial pressure. We hypothesize that endothelin may be a mediator of stretch-induced release of ANP.

Animals↗
PubMed1990

Effect of converting-enzyme inhibition on renal response to ANF in rats with experimental heart failure.

Increased activity of the renin-angiotensin system is thought to play a major role in the pathogenesis of salt retention and edema formation in congestive heart failure. The present study evaluates the effects of chronic inhibition of angiotensin-converting enzyme on the response to infusion of exogenous atrial natriuretic factor (ANF) in salt-retaining rats with chronic arteriovenous (a-v) fistula, an experimental model of high-output congestive heart failure. Administration of ANF in incremental doses (5-50 micrograms.kg-1.h-1) to Inactin-anesthetized, sham-operated control rats resulted in dose-dependent increases in urine flow, sodium excretion, and glomerular filtration rate, and significant decreases in mean arterial blood pressure. These effects of atrial peptide were markedly attenuated in salt-retaining rats with a-v fistula. However, chronic oral treatment with the angiotensin-converting-enzyme inhibitor enalapril restored the natriuretic response of sodium-retaining rats with a-v fistula to high doses of ANF. At a dose of 50 micrograms.kg-1.h-1, fractional excretion of Na (FENa) in a-v fistula rats given enalapril was 4.0 +/- 0.5%, which was significantly greater than that in a-v fistula rats without enalapril (0.5 +/- 0.4%, P less than 0.05) and not different from the response in sham-control rats (4.9 +/- 0.7%). The improvement in the natriuretic response after enalapril was not associated with a significant increase in GFR and occurred despite a decrease in mean arterial pressure. Moreover, chronic enalapril treatment did not significantly alter the plasma levels of immunoreactive ANF in either the sham controls or in the rats with a-v fistula.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Role of atrial appendages in modulating stimulated plasma atrial natriuretic peptide levels in conscious rats.

To evaluate the role of the atrial appendages in modulating plasma levels of atrial natriuretic peptide (ANP), we applied a series of both acute and chronic stimuli in conscious, chronic, bilaterally atrial-appendectomized (APP) and sham-operated control rats. Basal plasma ANP levels and urinary sodium excretion were normal in all rats after APP. The release of ANP was markedly blunted to acute volume expansion (+67% vs. +357% in controls, P less than 0.01) but was only moderately reduced after norepinephrine infusion (+106% vs. +212%, P less than 0.05) and was normal after acute salt load [+148% vs. +180% in controls, not significant (NS)]. Furthermore, plasma levels of ANP were increased normally in APP rats treated with deoxycorticosterone acetate (270 + 18 vs. 296 + 14 pg/ml in controls, NS) and in APP rats with congestive heart failure induced by a large arteriovenous (a-v) fistula between the aorta and the vena cava (306 +/- 18 vs. 302 +/- 12 pg/ml, NS). Sodium excretion patterns were similar in chronically stimulated APP and control rats. The results demonstrate that, although APP reduces the response of ANP release to acute volume expansion, it does not do so to other stimuli of either acute or chronic nature, suggesting that there is no permanent defect in the ability of APP rats to secrete ANP. These studies confirm that the atria are the major source for ANP release into the circulation after acute intravascular volume expansion. However, other tissue sources may contribute significantly to the levels of circulating ANP in response to this and other acute and chronic stimuli.

Animals↗